Author:

Janet Fricker

Introduction

The advent of breast cancer screening and advances in diagnostic imaging have resulted in the detection of many more breast lesions that cannot be felt manually (known as non-palpable) and are difficult to locate for surgeons. With early detection of cancer being critical for breast-conserving surgery, and incomplete excision being a big risk factor for recurrence of the cancer, a number of methods for locating precisely these ‘occult’ lesions were developed.

A standard method used since the 1960s is inserting a thin hooked wire into the lesion guided by ultrasound or stereotactic mammography just before surgery to guide the surgeon visually to the lesion. However, studies have reported high rates of tumour-affected margins around the lesion, which means patients have to undergo another operation to ensure the tumour is excised with clear margins.

Radioguided occult lesion localisation (ROLL) is an important alternative that is now widely used. Before surgery, a radiotracer is injected into the lesion using image guidance to direct the needle to the exact location. When surgeons make an incision into the breast, they are directed to the lesion using a gamma probe that pinpoints the radiation source.

The accuracy of ROLL for locating non-palpable lesions improves the rate of tumour margins clear of cancer and also allows the surgeon to minimise the amount of healthy breast tissue removed.

Nuclear medicine rises to the challenge

The idea for ROLL came from the nuclear medicine division at the European Institute of Oncology in Milan, Italy. The division, led by Giovanni Paganelli, was investigating the use of radiolabelling to track lymph drainage from breast tumours, work on which led to the sentinel lymph node biopsy (SNLB), which avoids unnecessary surgery on axillary lymph nodes where a biopsy of the sentinel node was cancer free.

That work was promoted by Umberto Veronesi, a pioneer of breast-conserving surgery, who had developed the quadrantectomy breast-conserving procedure (removal of only about a quarter of the breast) in the 1970s. Umberto Veronesi founded the European Institute of Oncology in 1994 and work on SLNB started in 1995. Paganelli remembers that the enthusiasm SLNB generated made it a talking point around the hospital.

The idea for ROLL came about almost by accident, remembers Paganelli, during a coffee break with his friend Alberto Luini, a breast surgeon. Luini challenged Paganelli to “solve with his high-tech methods” the problem of preoperative localisation of non-palpable breast lesions, just as nuclear medicine had played a crucial role in SLNB. Paganelli accepted the challenge.

From his sentinel node observations, Paganelli was aware that the majority of radiocolloids injected into the tumour did not migrate to lymph nodes. This property was not useful for locating sentinel nodes, which required the radiotracer to follow the lymph fluid as it drained away from the tumour. However, it was perfect for localising occult lesions, where the radiotracer needs to remains inside the tumour.

“In comparison to sentinel node we attached a bigger colloidal particle to ensure that the radioactivity didn’t come out of the tumour,” says Paganelli.

Measures of success

The radioactive tracer his team opted for was Tc-99m MAA (macroaggregated albumin). The first non-palpable breast lesion was injected under stereotactic guidance in 1996, and the lesion was removed surgically the following day.

A study published in 2001 showed that compared with using a wire, ROLL reduced the incidence of affected margins after excision. Another benefit was that there could be more time between the ROLL procedure and surgery, so reducing scheduling conflicts.

“ROLL allows surgeons to localise tumours more precisely, making surgery more accurate. This helps to facilitate lumpectomy in patients with small tumours,” says Paganelli. While there were initially concerns about radioactivity, he adds: “We undertook dosimetry studies for both sentinel node and ROLL showing that patients received less radioactivity than they would when flying from London to New York.”

ROLL has not replaced wire-guided localisation, which is still widely used, and there are other techniques in play, including some inspired by ROLL (radioactive seeds being one), and other cancers such as lung are under investigation for ROLL. But ROLL is in standard use at a number of institutions and is one of the key comparators in a growing number of localisation trials for effectiveness amid the global picture of breast-conserving surgery.